Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei 230001, China.
J Immunol Res. 2022 Aug 5;2022:7057089. doi: 10.1155/2022/7057089. eCollection 2022.
The commensal microbiota is involved in maintaining local pulmonary immune homeostasis under physiological conditions. Alterations in the amount and dominant species of the microbiota can reshape the immune response of the body and lead to a variety of lung diseases, including cancer. The precise mechanisms by which microbiota regulate immune cells during the progression of lung cancer remain obscure. In this study, using a mutated-driven spontaneous lung cancer mouse model, we found that the depletion of microbiota can alleviate lung lesions in -mutated mice at different stages of tumour development. Long-term antibiotic treatment significantly reduced the number NK cells and IFN- secretion and CD8T cells in the lungs of wild-type (WT) mice, suggesting that the microbiota plays an important role in maintaining homeostasis of NK cells and CD8T cells under normal conditions. However, in mutated mice, the altered pulmonary immune microenvironment resulted in a microbiota disorder and in the loss of the ability to regulate the immune responses of NK cells and CD8T cells, thus promoting the occurrence and development of lung cancer. Further mechanistic studies have shown that the CXCL9-CXCR3 axis participated in the local recruitment of NK cells and CD8T cells by the microbiota into lung tissues in -mutated mice. Our findings reveal the role of the microbiota in reshaping tumour-related immune responses involving NK cells and CD8T cells and shed light on the clinical immunotherapy of lung cancer.
共生微生物群在生理条件下参与维持肺部局部免疫稳态。微生物群的数量和优势物种的改变可以重塑机体的免疫反应，导致多种肺部疾病，包括癌症。微生物群在肺癌进展过程中调节免疫细胞的确切机制尚不清楚。在本研究中，我们使用突变驱动的自发性肺癌小鼠模型发现，在肿瘤发展的不同阶段，微生物群的耗竭可以减轻 -突变小鼠的肺部病变。长期抗生素治疗显著减少了野生型（WT）小鼠肺部 NK 细胞的数量和 IFN-的分泌以及 CD8T 细胞，这表明微生物群在正常情况下对于维持 NK 细胞和 CD8T 细胞的稳态发挥重要作用。然而，在 -突变小鼠中，改变的肺部免疫微环境导致微生物群紊乱，并丧失调节 NK 细胞和 CD8T 细胞免疫反应的能力，从而促进肺癌的发生和发展。进一步的机制研究表明，CXCL9-CXCR3 轴参与了微生物群将 NK 细胞和 CD8T 细胞募集到 -突变小鼠肺部组织中的局部过程。我们的研究结果揭示了微生物群在重塑涉及 NK 细胞和 CD8T 细胞的肿瘤相关免疫反应中的作用，并为肺癌的临床免疫治疗提供了线索。
